Glucose and lactose are common sugars found in our food. They serve a variety of functions, most notably energy storage and immune function. Under which conditions are the lac structural genes expressed most efficiently? What is the relative importance of automatic (e.g. transcription factors, transporters and others) and lipogenic processes for the synthesis of these sugars? What is the biochemistry of their metabolism and what roles do they play in cross-feeding between cells? Michael Dawson and John Harris, both of the University of Cambridge, summarized key issues on these types of animal sugars, with a focus on their metabolism. They also set out to explore the role of dietary components in determining glucose and lactose metabolism. In their review article, entitled “Seven lessons to be learnt about glucose and lactose”, they described the following seven points.
Seven Lessons To Be Learnt About Glucose And Lactose :
1. Glucose is a primary energy source for most animal cells.
Glucose metabolism in most animals is based on glycolysis, which involves the breakdown of glucose to pyruvate and lactate. This can be considered a “closed” system in tissues with higher metabolic rates, because lactate produced is used by those tissues. Lactate from tissues with low metabolic rates passes by way of the bloodstream to achieve feed forward regulation of cell metabolism.
In tissues with high metabolic rates, pyruvate can be formed from lactate by the addition of a two-carbon unit derived from acetyl-CoA. This is potentially a bottleneck if metabolism is based on glucose alone, because it means that both glycogen (4 carbon) and glycerol (3 carbon) need to be synthesized twice for every molecule of glucose when lactate is not produced.
2. Lactate is the most abundant fuel for heart and skeletal muscle.
The heart and skeletal muscle have a very high ratio of lactate to oxygen consumption, relative to all other tissues. These tissues have a much higher concentration of lactate transporters, including monocarboxylate transporter 1 (MCT1). This gives heart and skeletal muscle a much enhanced capacity to transport lactate and pyruvate into cells. Thus, these tissues are able to rapidly switch between aerobic and anaerobic metabolism despite the lack of alternative fuels. This is referred to as metabolic flexibility or “fuel switching”, which allows these tissues to use lactate produced by other tissues. This is particularly important in newborn animals, where high metabolic rates and lactate production persist.
3. Lactose is a major source of fuel for the colonic epithelium of mammals.
The relatively large quantities of lactose in milk are utilized as a carbon and energy source by the intestinal epithelium, which consists mainly of enterocytes and goblet cells. These cells express numerous hydrolytic enzymes including: β-galactosidase (lactase), α-galactosidase (α-Lac) and others. β-galactosidase breaks down lactose into glucose and galactose, which can be utilized in glycolysis.
4. Gene amplification of the lac operon is essential for lactose synthesis.
Lactose synthesis is a complex process involving 18 enzymes and at least nine transporters across the apical membrane of enterocytes. Gene amplification of the lac operon allows for highly efficient lactose synthesis within a small amount of DNA but with a large protein payload. For example, expression of β-galactosidase from the lac operon can result in up to 100,000 molecules formed per cell per minute.
These are proteolytically degraded and the released polypeptides are inserted by endocytosis into the apical surface of enterocytes. In addition to synthesis, lactose fermentation produces short chain fatty acids (SCFAs) that act as substrates for microbiota.
5. The age at which lactose tolerance is acquired is dependent on the feeding regime.
Lactose intolerance occurs when there is low expression of lactase (lacZ) in the intestinal mucosa and high amounts of glucose in the blood. This is a consequence of mutations in alpha-lactalbumin and/or lactase, which results in non-permissive mechanisms for microbial digestion. In contrast, high levels of lactase expression allow for the breakdown of milk and for the utilization of absorbed glucose. Lactose tolerance can be acquired through diet or childbirth, but both have little effect on expression levels. Babies are born with enough lactase to allow them to feed from colostrum and maternal breast milk.
However, lactose intolerance can develop in 3-4% of children worldwide by the age of 5 years. In contrast, lactose intolerance is rare in adults. The reason for this is that lactase expression increases over time during breast feeding and after weaning, so the first few weeks of life are critical in the development of lactose tolerance.
6. Lactose plays a key role in cross-feeding between cells.
Lactose from maternal milk is delivered to intestinal epithelial cells (IECs) by way of endocytosis and then metabolism for energy production or transferred to microorganisms located either on or within IECs. Through this process, lactose can also be transferred into other cells.
7. Glucose and lactate metabolism is regulated through crosstalk between cells.
Much of the cross-feeding in intestinal epithelial cells (IECs) occurs through glucose transporters (GLUTs) that are present in the apical membrane of enterocytes. GLUT types 1 and 4 are important in both glucose uptake and lactose transport. Several bacterial polysaccharides can inhibit GLUT function, therefore preventing lactose entry into IECs and reducing local concentrations of lactate.
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